New hope in treating progressive familial intrahepatic cholestasis in children

Abstract

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare, inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow (i.e., cholestasis), pruritus and progressive liver disease. Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive. The impaired bile flow within the liver, leads to accumulation in the liver and inflammation. Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive. A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion, with an aim to interrupt the enterohepatic circulation. These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids, reducing pruritus and liver injury and improving the patient quality of life. Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT). IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus. We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.

Keywords: Progressive familial intrahepatic cholestasis; Odevixibat; Intestinal bile acid transporter inhibitor; Maralixibat

Core Tip: Progressive familial intrahepatic cholestasis is a heterogenous autosomal recessive progressive cholestatic liver disease with varying genotype and phenotype. Identifying the underlying genetic disorder allows better understanding of the clinical phenotype and associated complications. Management is aimed at nutritional support, trying to make bile more hydrophilic by administering ursodeoxycholic acid and control of pruritus. Surgical biliary diversion has proved to reduce bile acid levels and improve pruritis in some patients. New hope exists with ileal bile acid transporter receptor inhibitors, however more data is still required. The ultimate treatment for end stage liver disease and persistent pruritus is liver transplantation.